Genome-wide Association of Yorkie with Chromatin and Chromatin-Remodeling Complexes

Abstract

SUMMARY The Hippo pathway regulates growth through the transcriptional co-activator Yorkie, but how Yorkie promotes transcription remains poorly understood. We address this by characterizing Yorkie’s association with chromatin, and by identifying nuclear partners that effect transcriptional activation. Co-immunoprecipitation and mass spectrometry identify GAGA Factor (GAF), Brahma complex, and Mediator complex as Yorkie-associated nuclear protein complexes. All three are required for Yorkie’s transcriptional activation of downstream genes, and GAF and the Brahma complex subunit Moira interact directly with Yorkie. Genome-wide chromatin binding experiments identify thousands of Yorkie sites, most of which are associated with elevated transcription, based on genome-wide analysis of mRNA and histone H3K4Me3 modification. Chromatin binding also supports extensive functional overlap between Yorkie and GAF. Our studies suggest a widespread role for Yorkie as a regulator of transcription, and identify recruitment of the chromatin modifying GAF protein and BRM complex as a molecular mechanism for transcriptional activation by Yorkie.

The Transcriptional Regulators TAZ and YAP Direct Transforming Growth Factor β-induced Tumorigenic Phenotypes in Breast Cancer Cells

“…Recent work has shown that TAZ/YAP recruit the nucleosome remodeling and deacetylation (NuRD) complex to repress gene expression (35). Yorkie (Yki), the homolog of TAZ/YAP in Drosophila melanogaster, is also known to associate with chromatin-modifying proteins (69,70). Thus, TAZ/YAP⅐TEAD complexes likely function directly to inhibit transcription in breast cancers through similar recruitment of repressive factors to control local chromatin remodeling at promoters.…”

Integrin signalling regulates YAP and TAZ to control skin homeostasis

“…Other co-factors of Yki/YAP that promote transcription include WBP2 (Zhang et al, 2011b), MASK1/2 (Sansores- Garcia et al, 2013;Sidor et al, 2013) and the SWI/SNF complex (Jin et al, 2013;Oh et al, 2013). The activity of Yki was found to be regulated by the Drosophila Hippo-Warts (Hpo-Wts) kinase signalling pathway, in which Wts directly phosphorylates Yki to promote its relocalisation from the nucleus to the cytoplasm (Dong et al, 2007;Huang et al, 2005;Oh and Irvine, 2008).…”

Hippo Component TAZ Functions as a Co-repressor and Negatively Regulates ΔNp63 Transcription through TEA Domain (TEAD) Transcription Factor

“…It is still unclear why the same TAZ-TEAD complex activates transcription of some cellular genes such as CTGF and Cyr61 but suppresses transcription of other genes such as ⌬Np63. Most interestingly, several recent studies have identified components of the chromatin/chromatin-remodeling complexes (BRM, MED mediator complexes, and SWI/SNF complexes) and histone methyltransferase (Ncoa6) complexes as binding partners of TAZ or its Drosophila homolog Yki (41,(57)(58)(59). Because these complexes control transcriptional status (activation or inactivation) of a specific gene, the methylation or acetylation status of chromatin on the promoter regions of a specific gene may determine the transcriptional activation or suppression functions of the TAZ-TEAD complex.…”